Aliera!ions in dopamine iransmission occur during drug abuse and addiction. To undcrstatid these changes, it is necessary lo first understand Ilie basic physicilugy that underlies dopamine transmission. The aim of this Pathway to Independence Award (K9WR(K)) proposal is to investigate the mechanisms of dopamine transmission while providing the candidate (Dr Christopher Ford) with the necessary nsentored training in electrophysiological and electrochemical techniques. The applicant has completed the K99 mentored phase ofthe award and has secured an indcfJcndent tenure Iract Assistant Professor jxisition in the Departmenl of Physiology and Biophysics at the Case Western Reserve University School ([unreadable]f Medicine. Having completed 2 of the three aims ofthe origninal research pro(X)sal and having met his initial career goal of becoming an independent investigator studying the cellular and molecular basis of addiction, this current pha.se ofthe proposal (R(X)) is designed to provide independent support that will I K used to further his studies, complete the remaining aims of the award and gain long-lemi ROI grant support. The central aim of this pro|M:[unreadable]sal is to dclcnnine the relationship between extracellular dopamine and i(s physiological consequences. The objective during die mentored pha.se will be to deiermine the mechanisms regulating dopamine transmission. The hypothesis to be le.sted is that dopamine mediates iransmission in the VTA in a tightly regulated, synaptic manner. The objeclive during the inde|>endent phase will be to define the concentration and duration of dopamine mediating transmission. The hypothesis being that transient, high concentrations of dopamine mediate transmission. A lack of knowledge ofthe basic mechanisms of dopamine transmission has hindered progre.s.s towards determining how transmission becomes dysregulated during [he course of drug addiction. Thus this work lias Ihe {xueniial to ideniiy and direct new strategies to treat tirug abuse and atldiction.